To report two cases of psychiatric symptoms associated with zonisamide, an antiepileptic drug, and raise clinical awareness of this potential adverse effect. Two male patients with epilepsy treated with zonisamide were retrospectively analyzed. Case 1 (25 years old) developed acute emotional and behavioral abnormalities (e.g., insomnia, aggression, incoherent speech) after switching from sodium valproate to zonisamide (200 mg/day). Case 2 (48 years old) had long-term zonisamide use (≥5 years) with persistent treatment-resistant psychotic symptoms (e.g., delusions, command hallucinations). Clinical courses, medication adjustments, and symptom responses were documented. In Case 1, psychiatric symptoms resolved after discontinuing zonisamide and switching to sodium valproate, with improved mood stability and reduced impulsivity. In Case 2, despite escalating antipsychotic medications (risperidone, clozapine), psychotic symptoms persisted, likely due to ongoing zonisamide use. Both cases highlighted zonisamide’s potential to exacerbate or induce psychiatric manifestations, possibly via mechanisms involving sodium/calcium channel inhibition and neurotransmitter dysregulation (e.g., dopamine, serotonin). Zonisamide can cause or worsen psychiatric symptoms, particularly in vulnerable individuals. Clinicians should monitor for mental health changes during zonisamide treatment and consider drug discontinuation or substitution with alternative antiepileptics (e.g., sodium valproate) if psychiatric adverse effects emerge. Awareness of this association is crucial to avoid misdiagnosis and optimize epilepsy management.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

ObjectiveTo explore the mechanism of Jiebiao Qingli decoction （JQD） in treating pneumonia caused by influenza A virus （IAV） infection. MethodsA total of 132 Balb/c mice were randomly assigned into normal control （NC）， model control （IAV）， oseltamivir （OSV， 37.5 mg·kg^-1）， and high-， medium-， low-dose JQD （H-， M-， and L-JQD： 6.05， 3.02， and 1.51 g·kg^-1， respectively） groups. The NC group was treated with normal saline nasal drops， and the other groups were intranasally inoculated with A/Brisbane/02/2018 （H1N1） ［pdm09-like virus （H1N1）］ for the modeling of IAV infection. Two hours post-modeling， the NC and IAV groups were administrated with normal saline by gavage， while other groups received corresponding drugs for 7 d. The body mass， survival status， and deaths of mice were recorded daily during the administration of the drugs. On days 3 and 7， the lung index was measured for mice in each group. Pathological changes in the lung tissue were observed via hematoxylin-eosin staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was conducted to measure the viral load （IAV-M） and the mRNA levels of Toll-like receptor 7 （TLR7）， p38 mitogen-activated protein kinase （p38 MAPK）， and nuclear factor-kappa B （NF-κB） in the lung tissue. Western blot was employed to measure the protein levels of p38 MAPK and NF-κB. Enzyme-linked immunosorbent assay was used to quantify serum levels of interleukin-2 （IL-2）， interleukin-6 （IL-6）， and tumor necrosis factor-alpha （TNF-α）. ResultsCompared with the NC group， the IAV group showed reduced survival quality and survival days （P<0.01）， lung congestion， inflammatory cell infiltration， elevated lung index （P<0.01）， increased viral load （P<0.01）， upregulated TLR7， p38 MAPK， and NF-κB levels （P<0.05， P<0.01）， decreased IL-2 level （P<0.01）， and elevated IL-6 and TNF-α levels （P<0.01）. Compared with the IAV group， H-JQD prolonged survival days （P<0.05）. All JQD groups alleviated pathological changes in the lung tissue and reduced the lung index （P<0.01）. M-JQD and H-JQD decreased the viral load （P<0.01）. H-JQD downregulated the mRNA levels of TLR7， p38 MAPK， and NF-κB （P<0.05， P<0.01） and the protein levels of p38 MAPK and NF-κB （P<0.01）， increased the serum IL-2 level （P<0.01）， and lowered the IL-6 and TNF-α levels （P<0.05， P<0.01）. M-JQD downregulated the mRNA level of NF-κB （P<0.01） and the protein level of p38 MAPK （P<0.05）， elevated the IL-2 level （P<0.01）， and lowered the TNF-α level （P<0.01）. ConclusionM- and H-JQD can prevent and control IAV infection-induced pneumonia dose-dependently by inhibiting the TLR7/MAPK/NF-κB signaling pathway， increasing IL-2， and reducing excessive secretion of IL-6 and TNF-α.

BACKGROUND:Rheumatoid arthritis is a chronic autoimmune disease.Early diagnosis is crucial for preventing disease progression and for effective treatment.Therefore,it is of significance to investigate the diagnostic characteristics and immune cell infiltration of rheumatoid arthritis. OBJECTIVE:Based on the Gene Expression Omnibus(GEO)database,to screen potential diagnostic markers of rheumatoid arthritis using machine learning algorithms and to investigate the relationship between the diagnostic characteristics of rheumatoid arthritis and immune cell infiltration in this pathology. METHODS:The gene expression datasets of synovial tissues related to rheumatoid arthritis were obtained from the GEO database.The data sets were merged using a batch effect removal method.Differential expression analysis and functional correlation analysis of genes were performed using R software.Bioinformatics analysis and three machine learning algorithms were used for the extraction of disease signature genes,and key genes related to rheumatoid arthritis were screened.Furthermore,we analyzed immune cell infiltration on all differentially expressed genes to examine the inflammatory state of rheumatoid arthritis and investigate the correlation between their diagnostic characteristics and infiltrating immune cells. RESULTS AND CONCLUSION:In both rheumatoid arthritis and normal synovial tissues,we identified 179 differentially expressed genes,with 124 genes up-regulated and 55 genes down-regulated.Enrichment analysis revealed a significant correlation between rheumatoid arthritis and immune response.Three machine learning algorithms identified LRRC15 and MICB as potential biomarkers of rheumatoid arthritis.LRRC15(area under the curve=0.964,95%confidence interval:0.924-0.992)and MICB(area under the curve=0.961,95%confidence interval:0.923-0.990)demonstrated strong diagnostic performance on the validation dataset.The infiltration of 13 types of immune cells was altered,with macrophages being the most affected.In rheumatoid arthritis,the majority of proinflammatory pathways in immune cell function were activated.Immunocorrelation analysis revealed that LRRC15 and MICB had the strongest correlation with M1 macrophages.To conclude,this study identified LRRC15 and MICB as potential diagnostic markers for rheumatoid arthritis,with strong diagnostic performance and significant correlation with immune cell infiltration.Machine learning and bioinformatics analysis deepened the understanding of immune infiltration in rheumatoid arthritis and provided new ideas for the diagnosis and treatment of rheumatoid arthritis.

Objective To investigate the therapeutic efficacy of artesunate(AS)on polycystic ovary syndrome(PCOS)in mice and explore the potential mechanism primarily.Methods Twenty-five female C57BL/6J mice were randomly divided into Control group,model group(PCOS group),low-and high-dose AS groups(AS15 and AS30 groups)and metformin group(Met group).In addition to the Control group,the mouse model of PCOS was established by subcutaneous injection of dehydroepiandrosterone(DHEA,60 mg/kg)following by a high-fat diet for 21 d.After modeling,AS of 15 and 30 mg/kg was intraperitoneally injected into the mice of the AS 15 and AS30 groups,respectively,and 200 mg/kg Met was given to those of the Met group by gavage,once per day,for 6 weeks.ELISA was used to detect serum testosterone(T),fasting insulin(FINS),luteinizing hormone(LH)and follicle-stimulating hormone(FSH),and the LH/FSH ratio was calculated.The levels of fasting blood glucose(FBG),triglyceride(TG)and total cholesterol(TC)were detected by automatic biochemical analyzer,and the homeostasis model assessment of insulin resistance(HOMA-IR)was calculated.The estrous cycle was observed,and HE staining was performed for pathological changes in the ovary and uterus.Immunofluorescence assay was employed to measure the expression of p-eIF2α,ATF4 and CHOP in the ovarian tissue.After steroidogenic human granulosa-like tumor cell line KGN were exposed to 100 μmol/L DHEA to simulate the hyperandrogen environment of PCOS,and then treated with 5 and 10 μg/mL AS for 24 h,the protein levels of endoplasmic reticulum stress signaling pathway was detected by Western blotting.Results Compared with the Control group,the PCOS mice had disturbed estrous cycle,polycystic changes in the ovaries,and significantly increased serum T level and LH/FSH ratio(P＜0.05),and obviously elevated HOMA-IR,TC and TG levels in terms of metabolism(P＜0.01).The expression levels of p-eIF2α,ATF4 and CHOP were notably up-regulated in the ovarian granulosa cells of PCOS mice and KGN cells after DHEA exposure(P＜0.05).Additionally,AS treatment attenuated the pathological changes of ovary and uterine expression,decreased the serum T level and the LH/FSH ratio(P＜0.05),and reduced HOMA-IR,TC and TG levels(P＜0.05)when compared with the PCOS mice.Moreover,the expression levels of p-eIF2α,ATF4 and CHOP were significantly down-regulated after AS treatment in both ovarian granulosa cells of PCOS mice and KGN cells(P＜0.05).Conclusion AS significantly improves glycolipid metabolic disorder and reproductive dysfunction in PCOS mice,which may be associated with its suppressing endoplasmic reticulum stress by inhibiting the PERK/eIF2α/ATF4/CHOP pathway.

OBJECTIVE To investigate the expression characteristics and regulatory mechanisms of the circadian clock gene period circadian regulator 1(PER1)and the tumor suppressor gene serine peptidase inhibitor Kazal type 5(SPINK5)in head and neck squamous cell carcinoma(HNSCC),and to elucidate the molecular mechanism by which PER1 regulates SPINK5 transcription via the NF-κB signaling pathway.METHODS Differentially expressed genes in HNSCC were screened using The Cancer Genome Atlas(TCGA)and GSE205155 datasets.The association between SPINK5 expression and patient prognosis was assessed via the GEPIA database.mRNA and protein expression levels of SPINK5 and PER1 in 60 clinical samples were detected by RT-qPCR,immunohistochemistry,and Western blot.PER1 knockdown(using siRNA)and overexpression(via plasmid transfection)were performed in the AMC-HN-8 cell line.Wound healing and colony formation assays were applied to evaluate the effects of PER1,SPINK5,and their interaction on HNSCC cell migration and proliferation.Western blot was utilized to examine the regulatory effect of NF-κB on SPINK5.RESULTS SPINK5 and PER1 were significantly downregulated in HNSCC tissues(all P<0.01),and their low expression was correlated with poor patient prognosis(for SPINK5,HR=0.69,P=0.006 7).A significant positive correlation was observed between PER1 and SPINK5 expression(R2=0.719 2,P=0.001 0).Knockdown and overexpression of PER1 respectively resulted in synchronous alterations in SPINK5 mRNA levels(all P<0.05).PER1 knockdown enhanced cell migration and proliferation(P<0.05),whereas SPINK5 overexpression suppressed these capabilities(P<0.01).Importantly,SPINK5 overexpression reversed the phenotypic changes induced by PER1 knockdown.Mechanistically,PER1 overexpression led to concomitant changes in NF-κB expression,activating the NF-κB pathway and thereby promoting SPINK5 transcription.CONCLUSION PER1 positively regulates SPINK5 transcription via the NF-κB pathway,inhibiting HNSCC cell proliferation and migration.These findings suggest that PER1 and SPINK5 may serve as potential therapeutic targets for HNSCC.

6-Thioguanine(6-TG)is an antineoplastic agent used in treatment of acute leukemia.However,significant interindividual variability in dosing regimens and frequent clinical manifestations of hepatotoxicity and myelosuppression as adverse effects have affected its therapeutic efficacy.Consequently,the development of rapid analytical methods for 6-TG in clinical samples,enabling continuous therapeutic drug monitoring of plasma concentrations,holds substantial significance in optimizing dosage regimens,mitigating adverse reactions,and investigating drug metabolism mechanisms.In this study,multi-tipped gold nanostars(AuNSs)were prepared.With bis-(p-sulfonylphenyl)phenylphosphine molecule as the protecting agent and internal standard molecule,the AuNSs were assembled onto a highly sensitive surface-enhanced Raman(SERS)substrate for developing a ratio-based SERS quantitative analysis method for 6-TG in serum.The AuNSs containing multiple tips and gaps exhibited strong local surface plasmon resonance effect and SERS activity,ensuring the sensitivity of the analytical method.Furthermore,the introduction of internal standard molecules could improve the reproducibility,which guaranteed this method suitable for rapid analysis of drug molecules in complex samples.Quantitative analysis of 6-TG was achieved with linear detetion range of 1.0×10?4-1.0 mmol/L.In the spiked recovery experiments of serum,the RSD was less than 5.32%,and the recoveries were 94%-104%,which proved that this method could be used for rapid quantitative determination of 6-TG in serum.This method provided a powerful tool for studying drug pharmacokinetics,which could promote the optimization of the usage methods of anti-cancer drugs,and it was expected to further enhance the clinical efficacy and safety of 6-TG,enabling it to achieve the best therapeutic effect.

OBJECTIVES: To evaluate the efficacy and safety of avatrombopag in promoting platelet engraftment after allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children, compared with recombinant human thrombopoietin (rhTPO). METHODS: A retrospective analysis was conducted on 53 pediatric patients who underwent allo-HSCT at the Institute of Hematology and Blood Diseases Hospital, Chinese Academy of Medical Sciences from April 2023 to August 2024. Based on medications used during the periengraftment period, patients were divided into two groups: the avatrombopag group (n=15) and the rhTPO group (n=38). RESULTS: At days 14, 30, and 60 post-transplant, platelet engraftment was achieved in 20% (3/15), 60% (9/15), and 93% (14/15) of patients in the avatrombopag group, and in 39% (15/38), 82% (31/38), and 97% (37/38) in the rhTPO group, respectively. There were no significant differences between the two groups in platelet engraftment rates at each time point, cumulative incidence of platelet engraftment, overall survival, and relapse-free survival (all P>0.05). Multivariable Cox proportional hazards analysis indicated that acute graft-versus-host disease was an independent risk factor for delayed platelet engraftment (P=0.043). CONCLUSIONS In children undergoing allo-HSCT, avatrombopag effectively promotes platelet engraftment, with efficacy and safety comparable to rhTPO, and represents a viable therapeutic option.
Humans ; Retrospective Studies ; Hematopoietic Stem Cell Transplantation/adverse effects* ; Male ; Female ; Child ; Child, Preschool ; Infant ; Adolescent ; Transplantation, Homologous ; Blood Platelets/drug effects* ; Thiazoles/therapeutic use* ; Thrombopoietin/therapeutic use* ; Thiophenes

The importance of gait assessment in the rehabilitation of cancer patients is gradually being recognized. However, quantitative analysis of balance ability in cancer patients is still limited. A total of 102 cancer patients meeting the inclusion criteria were recruited from Hefei Cancer Hospital, Chinese Academy of Sciences. Their balance ability was evaluated using the Berg Balance Scale (BBS). Gait data were collected by an electronic walkway and an IMU sensor system, including spatial-temporal and kinematic gait features such as step length, cadence, support time, and range of motion. Recursive feature elimination was used for feature selection. Ridge, Elastic Net, SVR, RF, and AdaBoost models were used to predict balance ability scores. Five-fold cross-validation was used to evaluate the performance of these models. Results show that the SVR model achieves the best performance with fifteen features (RMSE=3.22, R ²=0.91), followed by Ridge (RMSE=3.63, R ²=0.89). A method for evaluating balance ability based on gait features is proposed, providing a quantitative tool for personalized rehabilitation interventions in cancer patients.
Humans ; Postural Balance ; Neoplasms/rehabilitation* ; Gait ; Gait Analysis ; Biomechanical Phenomena ; Female